Thyrotropin-releasing hormone analogs and method of use

- Georgetown University

A series of novel thyrotropin-releasing hormone analogs wherein the C-terminal prolineamide moiety has been preserved, the N-terminal moiety comprises one of five different ring structures and the histidyl moiety is substituted with CF.sub.3, NO.sub.2 or a halogen. A method of use of the analog for the treatment of neurologic disorders is also provided.

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Claims

1. A compound having the following formula: ##STR9## wherein R" is selected from the group consisting of: ##STR10## R and R' are both I.

2. The compound of claim 1, wherein R" is ##STR11##

3. A compound having the following formula: ##STR12## wherein R and R' are respectively: (a) halogen and halogen;

(b) halogen and hydrogen;
(c) CF.sub.3 and hydrogen;
(d) hydrogen and CF.sub.3; or
(e) NO.sub.2 and hydrogen.

4. The compound of claim 1, wherein R" is ##STR13##

5. The compound of claim 1, wherein R" is ##STR14##

6. The compound of claim 1, wherein R" is ##STR15##

7. A method for the treatment of effects of neurologic damage in an animal, comprising administering to an animal suffering from neurologic damage a neurologic damage effect treating effective amount of a compound having the following formula: ##STR16## wherein R" is selected from the group consisting of: ##STR17## wherein R and R' are respectively: (a) halogen and halogen;

(b) halogen and hydrogen;
(c) CF.sub.3 and hydrogen;
(d) hydrogen and CF.sub.3; or
(e) NO.sub.2 and hydrogen,

8. A method for the treatment of effects of neurologic damage in an animal, comprising administering to an animal suffering from neurologic damage a neurologic damage effect treating effective amount of a compound having the following formula: ##STR18## wherein R" is selected from the group consisting of: ##STR19## wherein R and R' are respectively: (a) halogen and halogen;

(b) halogen and hydrogen;
(c) CF.sub.3 and hydrogen;
(d) hydrogen and CF.sub.3; or
(e) NO.sub.2 and hydrogen,

9. A method for the treatment of effects of neurologic damage in an animal, comprising administering to an animal suffering from neurologic damage a neurologic damage effect treating effective amount of a compound having the following formula: ##STR20## wherein R" is selected from the group consisting of: ##STR21## wherein R and R' are respectively: (a) halogen and halogen;

(b) halogen and hydrogen;
(c) CF.sub.3 and hydrogen;
(d) hydrogen and CF.sub.3; or
(e) NO.sub.2 and hydrogen,

10. The method of claim 7, wherein said animal is a human.

11. The method of claim 7, wherein R and R' are halogen and halogen.

12. The method of claim 11, wherein said halogens are selected from the group consisting of F, I and Br.

13. The method of claim 12, wherein said halogens are both the same.

14. A method for the treatment of effects of neurologic damage in an animal, comprising administering to an animal suffering from neurologic damage a neurologic damage effect treating effective amount of a compound having the following formula: ##STR22## wherein R" is selected from the group consisting of: ##STR23## wherein R and R' are are both I and wherein said neurologic damage is selected from the group consisting of brain trauma and spinal cord trauma.

15. The method of claim 7, wherein R and R' are halogen and hydrogen.

16. The method of claim 15, wherein said halogen is selected from the group consisting of F, I and Br.

17. The method of claim 7, wherein R and R' are CF.sub.3 and hydrogen.

18. The method of claim 7, wherein R and R' are hydrogen and CF.sub.3.

19. The method of claim 7, wherein R and R' are NO.sub.2 and hydrogen.

20. The method of claim 7, wherein R" is ##STR24##

21. A method for the treatment of effects of neurologic damage in an animal, comprising administering to an animal suffering from neurologic damage a neurologic damage effect treating effective amount of a compound having the following formula: ##STR25## wherein R and R' are respectively: (a) halogen and halogen;

(b) halogen and hydrogen;
(c) CF.sub.3 and hydrogen;
(d) hydrogen and CF.sub.3; or
(e) NO.sub.2 and hydrogen;

22. The method of claim 7, wherein R" is ##STR26##

23. The method of claim 7, wherein R" is ##STR27##

24. The method of claim 7, wherein R" is ##STR28##

Referenced Cited
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4426378 January 17, 1984 Holaday
4564609 January 14, 1986 Tamura et al.
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4906614 March 6, 1990 Giertz et al.
Foreign Patent Documents
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Other references
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Patent History
Patent number: 5686420
Type: Grant
Filed: Jan 27, 1995
Date of Patent: Nov 11, 1997
Assignee: Georgetown University (Washington, DC)
Inventor: Alan I. Faden (Mill Valley, CA)
Primary Examiner: Toni R. Scheiner
Assistant Examiner: Sheela J. Huff
Law Firm: Oliff & Berridge
Application Number: 8/379,797
Classifications
Current U.S. Class: 514/18; Tripeptides, E.g., Tripeptide Thyroliberin (trh), Melanostatin (mif), Etc. (530/331)
International Classification: A61K 3800; C07K 500; C07K 700; C07K 1700;